rs573002846

Variant names:

• chr11-22193299-G-A
• rs573002846
• NM_213599.3:c.-194G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-22193299-G-A
• chr11-22193299-G-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1 BS2_Supporting

The NM_213599.3(ANO5):​c.-194G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000424 in 941,202 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00058 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00042 (3 hom.)
• Consequence: ANO5 NM_213599.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 0 publications found

Genes affected

ANO5 (HGNC:27337): (anoctamin 5) This gene encodes a member of the anoctamin family of transmembrane proteins. The encoded protein is likely a calcium activated chloride channel. Mutations in this gene have been associated with gnathodiaphyseal dysplasia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

ANO5 Gene-Disease associations (from GenCC):

• gnathodiaphyseal dysplasia

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Orphanet
• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2L

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• Miyoshi muscular dystrophy 3

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000579 (22/37994) while in subpopulation SAS AF = 0.0166 (22/1324). AF 95% confidence interval is 0.0112. There are 1 homozygotes in GnomAd4. There are 15 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR,AD geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213599.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO5	NM_213599.3	MANE Select	c.-194G>A		5_prime_UTR	Exon 1 of 22	NP_998764.1	Q75V66
	ANO5	NM_001142649.2		c.-194G>A		5_prime_UTR	Exon 1 of 22	NP_001136121.1
	ANO5	NM_001410963.1		c.-194G>A		5_prime_UTR	Exon 1 of 21	NP_001397892.1	A0A804HL91

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO5	ENST00000324559.9	TSL:1 MANE Select	c.-194G>A		5_prime_UTR	Exon 1 of 22	ENSP00000315371.9	Q75V66
	ANO5	ENST00000682341.1		c.-194G>A		5_prime_UTR	Exon 1 of 21	ENSP00000508251.1	A0A804HL91
	ANO5	ENST00000684663.1		c.-194G>A		5_prime_UTR	Exon 1 of 21	ENSP00000508009.1	A0A804HKP2

Frequencies

GnomAD3 genomes AF: 0.000579 AC: 22 AN: 37998 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0165

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000417 AC: 377 AN: 903208 Hom.: 3 Cov.: 29 AF XY: 0.000604 AC XY: 255 AN XY: 422136

African (AFR) AF: 0.00 AC: 0 AN: 20658

American (AMR) AF: 0.00 AC: 0 AN: 8248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7662

East Asian (EAS) AF: 0.00 AC: 0 AN: 14520

South Asian (SAS) AF: 0.0140 AC: 344 AN: 24528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4604

Middle Eastern (MID) AF: 0.000506 AC: 1 AN: 1976

European-Non Finnish (NFE) AF: 0.00000380 AC: 3 AN: 789178

Other (OTH) AF: 0.000911 AC: 29 AN: 31834

GnomAD4 genome AF: 0.000579 AC: 22 AN: 37994 Hom.: 1 Cov.: 0 AF XY: 0.000796 AC XY: 15 AN XY: 18848

African (AFR) AF: 0.00 AC: 0 AN: 6932

American (AMR) AF: 0.00 AC: 0 AN: 5080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1078

East Asian (EAS) AF: 0.00 AC: 0 AN: 2362

South Asian (SAS) AF: 0.0166 AC: 22 AN: 1324

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 60

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 17936

Other (OTH) AF: 0.00 AC: 0 AN: 528

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.13
DANN	Benign	0.76
PhyloP100		-2.1
PromoterAI		-0.046	Neutral
Mutation Taster		=299/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs573002846; hg19: chr11-22214845;